Abstract
Smoking is a significant cause of preventable mortality worldwide. Understanding the neural mechanisms of nicotine addiction and smoking cessation may provide effective targets for developing treatment strategies. In the present study, we explored whether smokers have white matter alterations and whether these alterations are related to cessation outcomes and smoking behaviors. Sixty-six smokers and thirty-seven healthy non-smokers were enrolled. The participants underwent magnetic resonance imaging scans and smoking-related behavioral assessments. After a 12-week treatment with varenicline, 28 smokers succeeded in quitting smoking and 38 failed. Diffusion parameter maps were compared among the non-smokers, future quitters, and relapsers to identify white matter differences. We found that the future relapsers had significantly lower fractional anisotropy (FA) in the orbitofrontal area than non-smokers, and higher FA in the cerebellum than non-smokers and future quitters. The future quitters had significantly lower FA in the postcentral gyrus compared to non-smokers and future relapsers. Compared to non-smokers, pooled smokers had lower FA in bilateral orbitofrontal gyrus and left superior frontal gyrus. In addition, regression analysis showed that the left orbitofrontal FA was correlated with smoking-relevant behaviors. These results suggest that white matter alterations in smokers may contribute to the formation of aberrant brain circuits underlying smoking behaviors and are associated with future smoking cessation outcomes.